Genetic variations in TERT‐CLPTM1L locus are associated with risk of lung cancer in chinese population

Abstract

Recent genome-wide association studies (GWAS) have reported multiple genetic variations at 5p15.33 (TERT-CLPTM1L) associated with risk of lung cancer. However, most of the associated variations identified by GWAS thus far are unlikely to be the actual causal variants, but may be mostly marker-single nucleotide polymorphisms tagging functional variations that influence gene expression. This study aimed to explore the function-validated and potentially functional variations in TERT-CLPTM1L locus conferring susceptibility to lung cancer. A case-control study including 502 cases and 502 controls in Chinese Han population was firstly conducted. Bioinformatic approaches are applied to prioritize genetic variations based on their potential functionality. In the logistic regression analysis, TERT-rs2853669, rs2736108, and CLPTM1L-rs31490 were significant associated with increased risk of lung cancer (OR = 1.46, 95% CI = 1.22-1.75; OR = 1.22, 95% CI = 1.00-1.49 and OR = 1.74, 95% CI = 1.35-2.23 under additive model, respectively). The significant associations were observed in non-small-cell lung cancer but not-in-small-cell lung cancer, and more prominent in adenocarcinoma. Haplotype analysis presented a significant allele-dose effect of haplotypes in increasing risk of lung cancer (P for trend = 1.894 × 10(-6)). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of TERT-rs2853669, rs2736108, and CLPTM1L-rs31490, even after bonferroni correction for multiple comparisons (Pinteraction = 1.316 × 10(-9), 3.912 × 10(-4), and 2.483 × 10(-5), respectively). These findings indicated that the function-validated and potentially functional variations in TERT-CLPTM1L locus, modified by smoking, may play a substantial role in the susceptibility to lung cancer.

Expression level ofhTERTis regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma

“…This rs2853669 SNP is also associated with a risk for other cancer types, such as breast cancer and especially lung cancer in the Asian population. [11-13, 26] As summarized in Table 2, the Asian population has the highest A>G allele fraction, and the glioblastoma patients in the present study have significantly lower frequency of the T/T allele and higher T/C and C/C frequency. Considering the lower incidence of glioblastoma in the Korean population (age-standardized rate of 0.59 per 100,000 person-years)[27] compared with that in the United States (age-standardized rate of 3.19 per 100,000 person-years),[28] it would be interesting to determine the frequency of the T349C SNP in glioblastoma patients of other ethnic groups.…”

Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population

“…Yoo et al [16] showed that GG genotype of TERT rs2853669 A>G was significantly associated with increased lung cancer (LC) risk under a recessive model in the Korean population. Zhong et al [17] conducted a study for Chinese population and suggested that GG genotype of TERT rs2853669 A>G was also significantly associated with increased LC risk, especially with non-small lung cancer. Some other studies also reported the association of this gene with acute myeloid leukemia [18], prostate cancer [19] and breast cancer [20].…”

Polymorphisms in human telomerase reverse transcriptase (h TERT ) gene and susceptibility to gastric cancer in a Turkish population: Hospital-based case–control study

“…For example, Yoo et al (2015) showed that GG genotype of hTERT rs2853669 A>G was significantly associated with increased LC risk under a recessive model in the Korean population. In Chinese population, it was found that GG genotype of hTERT rs2853669 A>G was also significantly related with an increased risk of LC, especially in nonsmall lung cancer and more prominent in adenocarcinoma (Zhong et al, 2013). Moreover, Mosrati et al (2015) reported that GG genotype of hTERT rs2853669 A>G polymorphism was a risk factor for the acute myeloid leukemia in Swedish population.…”